Tobacco smoking continues to be the number 1 preventable cause of morbidity and mortality, contributing to millions of deaths every year and wreaking havoc on the welfare of families and communities worldwide. Although smokers are usually aware of smoking risks, they find quitting difficult due to the formidable grip of nicotine dependence (ND). So far, ND research has primarily focused on cigarettes, yet for many youth worldwide, tobacco addiction can be maintained by means other than the cigarette. In particular, over the past decade, water pipe (WP) smoking (a.k.a. hookah, shisha, narwhal) has dramatically become a worldwide phenomenon among youth. WP's worrisome trends have been monitored closely at the Syrian Center for Tobacco Studies (SCTS), where some of the pioneer evidence about its harmful and addictive properties was generated. Despite this, evidence-based solutions to the WP epidemic still lag behind. Obviously, interventions are needed to discourage WP initiation among youth, treat dependent WP smokers, and advance policy and product regulations. Unfortunately, this is hindered in part by the lack of knowledge on how ND develops and manifests in WP smokers. Characterizing ND in WP smokers will help guide the timing and composition of cessation treatments, as well as to counter deceptive product labeling, and drive public health policies to limit WP promotion and youth access. Most studies of ND in WP smokers to date are limited by cross sectional designs, instruments that are geared towards the cigarette, or failure to account for important personal and contextual factors. Thus, an approach that is rooted in common theoretical models of ND, and applies WP- sensitive tools within a longitudinal design has the potential of capturing the full spectrum of ND in young WP smokers. We will adopt this approach to test the following hypotheses: (1) symptoms of ND will appear despite intermittent use patterns in the majority of WP smokers and will predict important clinical outcomes (failed quitting, escalation), (2) the trajectory of ND inWP smokers differs from that of cigarette, and (3) the progression to ND in WP smokers is influenced by personal and contextual factors. For this purpose, we will recruit 250 WP smokers and nonsmokers susceptible to WP, and similar numbers for cigarettes, from 10th graders in Aleppo-Syria (H15 years at baseline) and follow them twice/year for 3 yrs. We plan to test these hypotheses by 1- detecting the first symptoms and diagnosis of ND among WP smokers, 2- comparing common trajectories of ND symptoms among WP smokers, cigarette smokers, and dual smokers, and 3- determining factors that predict ND development in young WP smokers. This project will allow us also to train researchers in Syria and the EMR in tobacco addiction science through a combination of training workshops, seed grants, and extended mentorship. We hope through this project to gain experience about ND in young WP smokers that can guide the development of interventions to reduce WP use and curtail WP-related morbidity and mortality. PUBLIC HEALTH RELEVANCE: This project addresses the knowledge gap about nicotine dependence in young water pipe smokers, in order to guide the development of interventions to reduce water pipe use and curtail WP-related morbidity and mortality.